Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells |
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Authors: | R Shringarpure T Grune KJA Davies |
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Institution: | (1) Ethel Percy Andrus Gerontology Center and Division of Molecular Biology, University of Southern California, 3715 McClintock Avenue, Los Angeles, California 90089-0191 (USA), Fax +1 213 740 6462, e-mail: Kelvin@usc.edu, US;(2) Neuroscience Research Center, Medical Faculty (Charité), Humboldt University, Berlin (Germany), DE |
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Abstract: | The generation of reactive oxygen species is an inevitable aspect of aerobic life. In addition to being exposed to free radicals
in the environment, aerobic organisms must also deal with oxygen radicals generated as byproducts of a number of physiological
mechanisms - for example, by the mitochondrial and endoplasmic reticulum electron transport chains, and by cells of the immune
system. Although most organisms are equipped with several lines of defense against oxidative stress, these defensive mechanisms
are not 100% effective, and oxidatively modified forms of proteins accumulate during aging, and in many pathological conditions.?Oxidatively
modified proteins can form large aggregates due to covalent cross-linking or increased surface hydrophobicity. Unless repaired
or removed from cells, these oxidized proteins are often toxic and can threaten cell viability. Mammalian cells exhibit only
limited direct repair mechanisms, and oxidatively damaged proteins appear to undergo selective proteolysis, primarily by the
major cytosolic proteinase, the proteasome. Interestingly, it appears that the 20S 'core' proteasome conducts the recognition
and elimination of oxidized proteins in an ATP-independent and ubiquitin-independent pathway.
Received 31 May 2001; accepted 26 June 2001 |
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Keywords: | , Protein oxidation, free radicals, proteolysis, proteasome, ubiquitin, apoptosis, |
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